The major focus of this grant renewal application is to probe further the reactivity and selectivity of a number of organic reactions in highly polar media such as 3.0-5.0 M lithium perchlorate-diethyl ether with applications to molecules of biological interest. This proposal is divided into three parts. The first part of this proposal concentrates on ionic Diels-Alder reactions with applications to the total synthesis of endiandric acid A, 11-oxosteroids, and lycopodine. All studies proposed in this area will be of a fundamental nature in order to define limits and scope of this potentially useful reaction. The second part focuses on cationic [5+2] cycloaddition reactions which have received only scant attention during the past 30 years despite the potential it holds for those engaged in the synthesis of natural and unnatural products. We have found that the yields can be dramatically improved by employing 3.0 M LiClO4-EtOAc in the presence of trimethylsilyl triflate. We propose to examine a number of inter- and intramolecular cationic [5+2] cycloaddition reactions in order to determine the generality of our findings. We propose to apply the above chemistry to the total synthesis of the novel non- steroidal estrogen, miroestrol. In addition we plan to prepare a number of bicyclo [5.3.1] systems related to taxol. In the final section, we will focus on completion of a synthesis of tabersonine and development of a novel approach to iboga alkaloids.